Biomedical subjects

G N Pierce

Publications and source records attributed to G N Pierce.

At least 91 records · Page 5Linked to original sources

PubMed1989

Effects of chronic swimming training on cardiac sarcolemmal function and composition.

Cardiac contractile function is dependent on the integrity and function of the sarcolemmal membrane. Swimming exercise training is known to increase cardiac contractile performance. The purpose of the present study was to examine whether a swimming exercise program would alter sarcolemmal enzyme activity, ion flux, and composition in rat hearts. After approximately 11 wk of exercise training, cardiac myosin and actomyosin Ca2+-adenosinetriphosphatase (ATPase) activity was significantly higher in exercised rat hearts than in sedentary control rat hearts. Glycogen content was increased in plantaris and gastrocnemius muscles from exercised animals as was succinic dehydrogenase activity in gastrocnemius muscle of exercised rats in comparison to sedentary rat preparations. Sarcolemmal vesicles were isolated from hearts of exercise-trained and control rats. Sarcolemmal Na+-K+-ATPase and K+-p-nitrophenylphosphatase activities, Na+-Ca2+ exchange, and passive Ca2+ binding did not differ between the two groups. ATP-dependent Ca2+ uptake and 5'-nucleotidase activity were elevated in the cardiac sarcolemmal vesicles isolated from exercised animals compared with sedentary control rats. Sarcolemmal phospholipid composition was not altered by the exercise training. Our results demonstrate that swimming training in rats does not affect most parameters of cardiac sarcolemmal function or composition. However, the elevated sarcolemmal Ca2+ pump activity in exercised rats may help to reduce intracellular Ca2+ and augment cardiac relaxation rates. The enhanced 5'-nucleotidase activity may stimulate adenosine production, which could affect myocardial blood flow. The present results further our knowledge on the subcellular response of the heart to swimming training in the rat.

Animals↗

PubMed1989

Cataract formation is prevented by administration of verapamil to diabetic rats.

The purpose of the present study was to examine the effects on cataractogenesis of daily sc administration of the Ca2+ antagonist drug verapamil to diabetic rats. Streptozotocin-induced diabetic rats were given verapamil half-way through the 8-week experimental period or during the full 8 weeks of diabetes. Verapamil administration had no effect on the high blood glucose values, low circulating insulin levels, or elevated triglyceride and cholesterol concentrations in the diabetic rats. Untreated diabetic rats had a 90% incidence of cataracts. Four weeks of verapamil administration reduced this incidence to 41%, and a full 8 weeks of drug treatment further lowered the incidence to 20%. Diltiazem, another Ca2+ antagonist, lowered the incidence of cataracts in the diabetic rats to a similar extent. Verapamil administration to the diabetic animals also partially protected against the presence of retinal microangiopathy in the diabetic animals. Lenticular hydration and lipid accumulation were only indirectly related to cataractogenesis in the diabetic rats and its protection by verapamil treatment. Lenticular electrolyte imbalance, particularly Ca2+, in the diabetic animals was closely correlated with cataract formation, and verapamil significantly reduced the alterations in these ion concentrations. The present results demonstrate the efficacy of verapamil as a protective agent against cataractogenesis and some retinal damage in diabetic animals. Most importantly, this occurs in the absence of any change in the glycemic status of the diabetic animals. The findings strongly support a role for lenticular Ca2+ imbalance in cataract development in diabetes and provide initial evidence to suggest its clinical use in the diabetic population at risk for blindness.

Animals↗

PubMed1989

Cardiac contracile protein ATPase activity in a diet induced model of noninsulin dependent diabetes mellitus.

The effects on cardiac function of feeding a diet high in sucrose to male Wistar rats over an extended period of time (15 months) was examined. This diet produced a diabetic condition which resembled noninsulin dependent diabetes mellitus. Resting hyperglycemia, high circulating insulin and triglyceride levels were observed in these animals. Further, the sucrose fed animals were overweight in comparison to chow fed control animals. Contractile protein Ca2+-ATPase activity was measured as a biochemical estimate of cardiac contractile function. Myosin and actomyosin Ca2+-ATPase activities of isolated myofibrillar fractions from hearts of experimental animals were depressed in comparison to chow fed control rats. Myosin K+-EDTA activity was also altered. The results demonstrate for the first time a defect in contractile protein Ca2+-ATPase activity in rat hearts using a model of noninsulin dependent diabetes mellitus. As the animals were euthyroid, thyroid hormone alterations in these animals were unlikely to influence the results. The results also demonstrate that insulin could not be a direct factor associated with cardiac pathology in diabetes. Instead, cardiac dysfunction may be associated with other, as yet undefined, metabolic abnormalities which accompany the diabetic state.

Animals↗

PubMed1988

Stimulation of sodium-calcium exchange by cholesterol incorporation into isolated cardiac sarcolemmal vesicles.

Modification of the cholesterol content of highly purified cardiac sarcolemma from dog ventricles was accomplished by incubation with phosphatidylcholine liposomes containing various amounts of cholesterol. The degree of cholesterol enrichment could be varied by changing the liposomal cholesterol/phospholipid ratio or varying the liposome-membrane incubation time. Na+-Ca2+ exchange measured in cholesterol-enriched sarcolemmal vesicles was increased up to 48% over control values. The stimulation of Na+-Ca2+ exchange was associated with an increased affinity of the exchanger for Ca2+ (Km = 17 microM compared with Km = 22 microM for control preparations). Na+-Ca2+ exchange measured in cholesterol-depleted membrane preparations was decreased by 15%. This depressed activity was associated with a decreased affinity of the exchanger for Ca2+ (Km = 27 microM). These changes were not due to either a change in membrane permeability to Ca2+ or an increase in the amount of Ca2+ bound to sarcolemmal vesicles. The stimulating effect of cholesterol enrichment was specific to the Na+-Ca2+ exchange process since sarcolemmal Ca2+-Mg2+ ATPase activity was depressed 40% by cholesterol enrichment. Further, K+-p-nitrophenylphosphatase and Na+-K+ ATPase activities were depressed in both cholesterol-depleted and cholesterol-enriched sarcolemmal vesicles. In situ oxidation of membrane cholesterol completely eliminated Na+-Ca2+ exchange. These results suggest that cholesterol is intimately associated with Na+-Ca2+ exchange and may interact with the exchange protein and modulate its activity.

4-Nitrophenylphosphatase↗

PubMed1988

Beneficial effects of verapamil in diabetic cardiomyopathy.

It has been suggested that the occurrence of an intracellular Ca2+ overload may result in the development of diabetic cardiomyopathy, which is associated with depletion of high-energy phosphate stores and a derangement of ultrastructure and cardiac dysfunction. Accordingly, the effects of verapamil, a Ca2+ antagonist, on cardiac function, ultrastructure, and high-energy phosphate stores in the myocardium were evaluated in rats made diabetic by an intravenous injection of streptozocin (65 mg/kg). Four weeks after the induction of diabetes, the animals were treated with three doses (2, 4, or 8 mg.kg-1.day-1) of verapamil for 4 wk until they were used for the measurement of different parameters. Untreated diabetic animals had slower heart rates, depressed rate of contraction and rate of relaxation, lower peak left ventricular systolic pressure, and elevated left ventricular diastolic pressure. All of these changes were significantly improved in diabetic rats receiving verapamil treatment. The beneficial effects of verapamil were more evident with higher doses (8 mg.kg-1.day-1) than with the lower doses (2 mg.kg-1.day-1). The diabetic animals also showed alterations in myocardial high-energy phosphate stores and exhibited evidence of ultrastructural damage; these abnormalities were improved by verapamil treatment without affecting their hyperglycemic status. Our results demonstrate that verapamil is capable of preventing diabetes-induced myocardial changes and support the involvement of Ca2+ in the cardiac pathology during diabetes.

Adenosine Diphosphate↗

PubMed1987

Cationic interactions with Na+-H+ exchange and passive Na+ flux in cardiac sarcolemmal vesicles.

Na+-H+ exchange and passive Na+ flux were investigated in cardiac sarcolemmal vesicles as a function of changing the ionic composition of the reaction media. The inclusion of EGTA in the reaction medium resulted in a potent stimulation of Na+ uptake by Na+-H+ exchange. It was found that millimolar concentrations of Mg2+ and Li+ were capable of inhibiting Na+-H+ exchange by 80%. One mechanism by which these ions may inhibit intravesicular Na+ accumulation by Na+-H+ exchange is via an increase in Na+ efflux. An examination of Na+ efflux kinetics from vesicles pre-loaded with Na+ revealed that Na+, Ca2+, Mg2+ and Li+ could stimulate Na+ efflux. Na+-H+ exchange was potently inhibited by an organic divalent cation, dimenthonium, which screens membrane surface charge. This would suggest that Na+-H+ exchange occurs in the diffuse double layer region of cardiac sarcolemma and this phenomenon is distinctly different from other Na+ transport processes. The results in this study indicate that in addition to a stimulation of Na+ efflux, the inhibitory effects of Mg2+, Ca2+ and Li+ on Na+-H+ exchange may also involve a charge dependent screening of Na+ interactions with the membrane.

Animals↗

PubMed1987

Trans-sarcolemmal Ca2+ movements associated with contraction of the rabbit right ventricular wall.

The purpose of this study was to examine the movements of Ca2+ into the myocardium from the extracellular space during the course of muscle contraction. Equilibration of the rabbit right ventricular wall with perfusate containing 45Ca was measured by collecting effluent droplets over time. This protocol was carried out in a quiescent muscle and then repeated 15-20 minutes later in an identical fashion except that halfway through the collection period the muscle was stimulated to contract. We were thus able to quantitate the contraction-dependent changes in 45Ca movements. In control experiments using [58Co]EDTA as an extracellular space marker, we observed that contraction altered the volume of this space. This alteration in extracellular space was relatively small, and the quantitation of 45Ca movements was corrected for this change. The addition of 1 microM Bay K 8644 to the perfusate stimulated tension and augmented Ca2+ depletion from the extracellular space. The addition of 15 microM nifedipine to the perfusate significantly reduced both tension development and Ca2+ depletion from the extracellular space of the muscle. Net contraction-dependent movement of Ca2+ from the extracellular space into the myocardium under control conditions at 1 mM [Ca2+] was 10-14 mumol Ca2+/kg tissue wet wt/beat. This value indicates either a large contribution of Ca2+-induced Ca2+ release from the sarcoplasmic reticulum and/or significant contribution of sarcolemmal bound Ca2+ to excitation-contraction coupling in the rabbit ventricle.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

PubMed1986

Role for sulfur-containing groups in the Na+-Ca2+ exchange of cardiac sarcolemmal vesicles.

Different amino acid residues in cardiac sarcolemmal vesicles were modified by incubation with various chemical reagents. The effects of these modifications on sarcolemmal Na+-Ca2+ exchange were examined. Dithiothreitol, an agent that maintains sulfur-containing residues in a reduced state, caused a time- and concentration-dependent decrease in Na+-Ca2+ exchange. The treatment with dithiothreitol resulted in a decrease in Vmax values but did not alter the Km for Ca2+ for the Na2+-Ca2+ exchange reaction. If Na+ replaced K+ as the ion present during the modification of sarcolemmal membranes with dithiothreitol, there was substantially less of an inhibitor effect on Na+-Ca2+ exchange. Similar results were obtained with reduced glutathione, a reagent that also maintains sulfur-containing residues in a reduced state. Two sulfhydryl modifying reagents, methylmethanethiosulfonate and N'-ethylmaleimide, were capable of altering Na+-Ca2+ exchange, and the type of ion present during modification significantly affected the extent of this alteration. Almost all of the chemical reagents investigated that modified other amino acid resides (carboxyl, lysyl, histidyl, tyrosyl, tryptophanyl, arginyl and hydroxyl) had the capacity to alter Na+-Ca2+ exchange after preincubation with the sarcolemmal membrane vesicles. However, the sulfur residue-modifying reagents were the only compounds to exhibit significant differences in their action on Na+-Ca2+ exchange, depending on whether Na+ or K+ was present in the preincubation modification medium. The tryptophan modifier, N-bromosuccinimide, was the sole reagent that elicited a substantial increase in membrane permeability. The evidence is consistent with the hypothesis that sulfur-containing residues interact with a Na+-binding site for Na+-Ca2+ exchange in cardiac sarcolemmal vesicles.

Animals↗

PubMed1986

Adriamycin stimulates low-affinity Ca2+ binding and lipid peroxidation but depresses myocardial function.

Studies have been performed to examine the effects of different concentrations of adriamycin (10(-9)-10(-3) M) on sarcolemmal ATP-independent Ca2+ binding, contractility, ultrastructure, energy [ATP and creatine phosphate (CrP)] stores, and lipid peroxide activity in the rat myocardium. Low-affinity Ca2+ binding was stimulated, whereas high-affinity Ca2+ binding was inhibited by adriamycin in sarcolemmal vesicles isolated from ventricles. These alterations were accompanied by changes in the number of Ca2+ binding sites without affecting the membrane affinity for Ca2+. Peak developed force as well as positive and negative dF/dt in the isolated papillary muscle were depressed. The percent changes in contractility due to adriamycin were not affected by extracellular Ca2+ concentration. Ultrastructural changes in the papillary muscles due to adriamycin included mitochondrial swelling, presence of intramitochondrial granules, increased lysosomes, and disruption of myofibrils. ATP and CrP content of the papillary muscles was significantly reduced by the drug. Lipid peroxides, estimated by quantitating malondialdehyde content, were elevated by adriamycin. Most of these changes due to adriamycin became apparent at 10 microM or higher concentrations of the drug, and the maximum effect was seen at 1 mM of adriamycin. The in vitro depressant effect of adriamycin may not be related to changes in the low-affinity Ca2+ binding sites, but instead it appears to be associated with a lower energy state and myocardial cell damage.

Adenosine Triphosphate↗

PubMed1985

Na+-H+ exchange in cardiac sarcolemmal vesicles.

The transport of Na+ by a purified sarcolemmal vesicular preparation from canine ventricular tissue was studied as a function of both internal and external pH. The uptake of Na+ into sarcolemmal vesicles increased upon raising the extravesicular pH of the reaction medium. Half-maximal uptake of Na+ was observed at a pHo of about 8.1 and maximal uptake occurred at pH 8.6. The uptake of Na+ by sarcolemma was also dependent upon the intravesicular pH. Na+ uptake into sarcolemmal vesicles was greatly attenuated in the absence of a H+ gradient across the membrane. Transport of Na+ was potently inhibited by amiloride, a known blocker of Na+-H+ exchange. LiCl was also an effective inhibitor of Na+ transport. In the presence of optimal H+ gradients, Na+ uptake was linear for the first 5 seconds of the reaction and exhibited a Vmax of 290 nmol Na+/mg per min and a KNa of 3.5 mM. These experiments strongly indicate the presence of a Na+-H+ exchange system in cardiac sarcolemma. This activity appeared to be relatively specific for this membrane fraction. The identification of Na+-H+ exchange activity in a sarcolemmal vesicular fraction from the heart will permit extensive characterization of the regulation and kinetics of this antiporter in future investigations.

Amiloride↗

PubMed1985

Binding of glycolytic enzymes to cardiac sarcolemmal and sarcoplasmic reticular membranes.

Glyceraldehyde-phosphate dehydrogenase and phosphoglycerate kinase activities were associated with a particulate fraction in a cardiac homogenate preparation. NaCl treatment displaced these activities from the particulate fraction. These membrane-associated glycolytic enzymes were gradually lost during the rigorous isolation procedures needed to purify sarcolemmal and sarcoplasmic reticular vesicles. However, exogenously added enzymes did bind to these purified membranes in relatively large quantities (glyceraldehyde-phosphate dehydrogenase: 1.14 mg of enzyme/mg of sarcolemma, 0.30 mg of enzyme/mg of sarcoplasmic reticulum; phosphoglycerate kinase: 1.02 mg of enzyme/mg of sarcolemma, 0.12 mg of enzyme/mg of sarcoplasmic reticulum), which suggests a nonspecific type of binding interaction. Approximately 50% of the glyceraldehyde-phosphate dehydrogenase and 90% of the phosphoglycerate kinase were inactivated upon binding. NaCl removed the enzyme from the membranes in a concentration-dependent manner similar to its effects in the particulate fraction. Dimethonium (5 mM), an organic divalent cation which screens membrane-surface charge, removed greater than 90% glyceraldehyde-phosphate dehydrogenase from the sarcolemmal membrane. These results, and those with NaCl, suggest that the binding of the enzyme to the membrane is charge-related. Phospholipids extracted from the sarcolemmal membrane were capable of binding and inactivating both glycolytic enzymes. Purified anionic phospholipids were more potent at binding and inactivating both enzymes than were neutral phospholipids. These data show that glyceraldehyde-phosphate dehydrogenase and phosphoglycerate kinase can bind to sarcolemmal and sarcoplasmic reticular membranes. This binding is reversible, charge-dependent, and inhibitory. This binding is likely to involve anionic membrane phospholipids.

Animals↗

PubMed1985

Adaptive changes in subcellular calcium transport during catecholamine-induced cardiomyopathy.

Rats were injected intraperitoneally with isoproterenol in dosage of 40 mg/kg body weight and heart microsomal and mitochondrial fractions were isolated 3, 9 and 24 h later. The heart/body weight ratio increased at 9 and 24 h after injection without any changes in the yield of subcellular organelles. Microsomal calcium uptake was significantly elevated at 3 h but returned to normal at 9 h and then became depressed 24 h post-injection. Mitochondrial calcium uptake was significantly increased 9 and 24 h after isoproterenol administration. Kinetic parameters of the calcium transport function indicated that the apparent affinity for Ca2+ remained unchanged, whereas Vmax values were altered in the experimental groups. Although there was no significant change in the phospholipid composition, the total phospholipid contents were increased (at 3, 9 and 24 h for microsomes; 3 and 9 h for mitochondria) in both types of organelles. The protein composition, as determined by gel electrophoresis, was altered in microsomes, but not in mitochondria. These results demonstrate rapid structural and functional changes in subcellular organelles. Such alterations may play an adaptive role in maintaining the intracellular calcium homeostasis during the development of catecholamine-induced cardiomyopathy.

Animals↗

PubMed1985

Passive calcium-buffering capacity of a rabbit ventricular homogenate preparation.

This study characterizes the passive Ca2+-binding capacity of a crude homogenate fraction prepared from rabbit ventricular tissue. The soluble and particulate fractions of the homogenate were separated by centrifugation, and the Ca2+-binding capacity of each fraction was measured separately with Ca2+-selective electrodes and then summed to obtain the Ca2+-binding capacity of the total tissue homogenate. Qualitatively, the Ca2+ bound to the homogenate exhibited both relatively high- (Km less than 1 microM) and low-affinity (Km greater than 10 microM) sites over the physiological range of free Ca2+ concentrations. The total homogenate bound 72, 128, and 308 mumol Ca2+/kg wet wt tissue at 1, 10, and 50 microM free Ca2+ concentrations, respectively. The Ca2+ bound to the homogenate was mostly La3+ displaceable, which suggests that it represents a largely noncompartmentalized, rapidly exchangeable fraction of Ca2+. Myofibrillar ATPase activity was examined as a function of free Ca2+ concentration in an ionic medium similar to that used in the Ca2+-binding experiments. At free Ca2+ concentrations that stimulated myofibrillar ATPase activity half maximally, the measured rise in Ca2+ bound to the homogenate above resting values was greater than 100 mumol/kg wet wt. These data provide base-line values for the passive Ca2+-buffering capacity of the myocardium, although relevance to the physiological setting must be interpreted with caution.

Adenosine Triphosphatases↗

PubMed1985

Mechanisms of the defect in cardiac myofibrillar function during diabetes.

Diabetes was induced in rats by an intravenous injection of streptozotocin (65 mg/kg body wt), and animals were killed 8 wk later. Some animals were maintained in a diabetic state for 6 wk and then given 2 wk of insulin treatment in vivo. Myofibrils were isolated and ATPase activities measured. Mg2+-ATPase and Ca2+-stimulated ATPase activities were depressed in diabetic rat hearts in comparison to control; insulin treatment normalized these activities. The depression in myofibrillar ATPases was of gradual onset as no changes were detected 2 wk after inducing diabetes. Treatment of diabetic animals with thyroid hormone did not restore changes in myofibrillar ATPase activities. Marker enzyme activities did not reveal any detectable contamination by cardiac membranes. Mg2+-ATPase activity of myofibrillar preparations from control and diabetic hearts responded differently to N-ethylmaleimide modification. Furthermore, myofibrillar sulfhydryl reactivity to 5,5'-dithiobis(2-nitrobenzoic acid) was significantly depressed in diabetic preparations in comparison to control and insulin-treated diabetic animals. These results suggest that the defect in myofibrillar ATPase activities in chronic diabetes may be due to some modification of sulfhydryl groups.

Adenosine Triphosphatases↗

PubMed1985

Modification of the function of cardiac subcellular organelles by insulin.

Although insulin is known to elicit a positive inotropic effect in cardiac-muscle preparations, little is known concerning the mechanism responsible for this action. Because various subcellular organelles such as mitochondria, sarcoplasmic reticulum (SR), sarcolemma, and myofibrils are intimately involved in determining the cardiac contractile function, the effects of insulin (0.1-1000 mU/ml) on some selected enzymatic activities associated with these organelles were investigated. Insulin significantly enhanced Ca2+ uptake and Ca2+-stimulated ATPase activities of SR preparations obtained by two different methods. Insulin had no effect on mitochondrial Ca2+ uptake and ATPase activities or myofibrillar ATPase activities. Sarcolemmal Na+, K+-ATPase activity was stimulated only in the presence of 1 U/ml insulin, whereas sarcolemmal Ca2+ pump activity was increased by all insulin concentrations employed. Sarcolemmal Ca2+-ATPase activity and ATP-independent Ca2+ binding were augmented in the presence of 1 U/ml insulin only. These subcellular effects of insulin, either alone or in concert, may partially explain the positive inotropic action of insulin.

Adenosine Triphosphatases↗

PubMed1985

Heart mitochondrial function in chronic experimental diabetes in rats.

Diabetes was introduced in rats by an intravenous injection of streptozotocin (65 mg/kg). Animals were sacrificed 8 weeks later and mitochondria were isolated from the ventricular tissue by differential centrifugation. The state 3 respiration, oxidative phosphorylation rate and Mg2+-dependent ATPase activities were depressed in mitochondria from diabetic hearts. These changes were partially reversible upon 2 weeks of insulin and fully reversible after 4 weeks of insulin therapy. Mitochondrial calcium uptake but not calcium binding, was decreased in diabetes and this change was fully reversible by 2 weeks of insulin administration. The observed alterations in mitochondrial function could not be explained on the basis of any changes in mitochondrial lipid and protein composition or subcellular contamination. These results indicate the presence of a generalized depression in mitochondrial function in chronic diabetes and such a defect is suggested to contribute in the development of cardiomyopathy at late stages of diabetes.

Animals↗

PubMed1984

Alterations in adenylate cyclase activity due to streptozotocin-induced diabetic cardiomyopathy.

The effect of chronic experimental diabetes on the adenylate cyclase system (AC) in the rat heart was investigated. Rats were made diabetic by an intravenous injection of streptozotocin (65 mg/kg), hearts were removed 8 weeks later and washed cell particles were isolated. AC activity was measured in the absence and presence of different concentrations of forskolin, NaF, GTP analogue [Gpp(NH)p] or epinephrine. A significant depression in the epinephrine stimulated AC activity was observed in diabetic hearts. Basal AC activity and stimulation of AC with forskolin, NaF and Gpp(NH)p were not significantly different between control and diabetic preparations. These results indicate no apparent alterations in the regulatory or catalytic properties of AC in hearts from chronic diabetic rats. The observed depression in epinephrine stimulated AC activity may account for the depressed inotropic action of catecholamines in the diabetic cardiomyopathy.

Adenylyl Cyclases↗

PubMed1984

Sarcolemmal alterations during the development of genetically determined cardiomyopathy.

The purpose of this study was to identify alterations in specific enzyme and Ca2+ binding activities in cardiac sarcolemmal fractions from UM-X7.1 myopathic Syrian hamsters during the development of cardiomyopathy. Experimental and healthy control animals were examined from 25 to 200 days of age. Sarcolemmal Na+, K+-ATPase activity was depressed in the myopathic hamsters throughout the time course of this study. Sarcolemmal ATP-independent Ca2+ binding was found to be depressed in experimental animals as early as 55 days of age. Ca2+ -stimulated, Mg2+ -dependent ATPase activity was depressed in the experimental animals by 90 days of age and this decrease in enzyme activity was accompanied by a decrease in ATP-dependent Ca2+ binding capacity of the sarcolemmal membranes. Mg2+ -ATPase and Ca2+ -ATPase activities were only affected in the latter stages of the disease (155 to 200 days old). NaF, epinephrine and Gpp(NH)p stimulation of the sarcolemmal adenylate cyclase activity was also observed to be attenuated during the latter stages of the disease. These defects in adenylate cyclase system of the sarcolemmal fraction appeared specific since basal adenylate cyclase activity was not altered at any age studied. The results demonstrate that the earliest lesions in sarcolemmal activity in myopathic hamster heart occur in Na+, K+-ATPase and ATP-independent Ca2+ binding capacity. These defects correspond temporally to the initial stages of cardiac necrotic development in this strain of myopathic hamster.

Adenosine Triphosphatases↗